Opportunities and Limits of the Use of Azides in Industrial Production. Implementation of Safety Measures

Abstract

Azides are very versatile precursors of organic synthesis functionalities such as amines, isocyanates, sulfonamides, triazoles, tetrazoles, triazolines, aziridines, amino acids and diazo compounds. In industry, one of the favourite starting materials for these syntheses is sodium azide which can generate hydrazoic acid whose toxicity and detonation potential is of major safety concern. However sodium azide is used daily in large tonnage in the air-bags of vehicles, in biologic institutes as a bactericide and in agriculture as a herbicide. In industrial synthesis, sodium azide is actually the starting material of herbicides, anti-HIV pharmaceuticals, anti-pain compounds and hypo tensors. This massive use of sodium azide represents severe toxicological and physical damage risks. The industrial synthesis under the scope of this presentation will be the manufacture of a tetrazole produced in several tens of tons per year. A risk assessment concluded that it would be necessary to conduct the reaction in a 'Bunker' and to minimise risks by absolutely avoiding generation of hydrazoic acid. This can be achieved by a careful design of the process and by strict organisational measures. Furthermore, the reaction equipment was designed to prevent any condensation of hydrazoic acid. One way to prevent its formation is to maintain the reaction medium under basic conditions at all times. This is achieved by using triethylamine hydrochloride as a buffer. In the applied reaction conditions it could be demonstrated that triethylamine was the refluxing compound at 130 °C and that a thermally stable triethyl ammonium azide was formed. The environmental problem could be resolved by incineration of the wastewaters. In conclusion, reactions with sodium azide are safe, they only need a stabilising agent. A search for such compounds could be an interesting but rather dangerous research project.

9.03 Organic Synthesis in Small Scale Continuous Flow: Flow Chemistry

“…33 Unfortunately, HN 3 is extremely toxic (comparable to HCN) and owing to the explosive nature and low boiling point (37 1C) of this high-energy material, [34][35][36] procedures involving free HN 3 have not found many practical applications.…”

Synthesis of Heterocycles by Intramolecular Cyclization of Organic Azides

“…Among these processes the use of transition metal catalyzed organic azide transformations surely deserves a close inspection. Although one of the main safety concern about the industrial use of azide is the toxicity and detonation potential of hydrazoic acid that can be released [99], the stability of this reactive molecules is dramatically increased when the number of carbon atoms in the organic azide exceed the number of nitrogen atoms. Their use is associated with a high synthetic versatility that allows for the generation of the very reactive nitrene unit, "RN", with the eco-friendly nitrogen being the only side product.…”

Tin‐Catalyzed Synthesis of 5‐Substituted 1H‐Tetrazoles from Nitriles: Homogeneous and Heterogeneous Procedures

“…Therefore, the synthesis and functionalization of 5‐substituted 1 H ‐tetrazoles have been widely studied and numerous procedures have been reported and reviewed . Due to the hazards encountered with the use of hydrazoic acid, most of them involve the [3+2] cycloaddition of an azide anion to a nitrile in the presence of an acid. The cycloaddition presents a high activation barrier which prompted researchers to use additives or catalysts for milder experimental conditions.…”